The Function of Neuroendocrine Cells in Prostate Cancer

Abstract

Abstract : Purpose: The goal of the project is to determine the function of neuroendocrine (NE) cells in the initiation and progression of human prostate cancer Scope: 1) Use a pten null mouse prostate cancer model to determine if ablation of NE cells by selective expression of a toxin in these cells can delay or prevent tumor initiation and/or progression. 2) Use a human tissue recombination model to determine if depletion of NE cells from human epithelial cells can retard the initiation and progression of the recombinant tumor. 3). Demonstrating the origin and molecular basis of human small cell carcinoma Major findings: 1) We have established a robust protocol to procure fresh human prostate tissue and isolate subpopulations of prostatic epithelial cells; 2) We have identified the appropriate combinations of cell surface markers for the isolation of NE cells; 3) We have demonstrated that neuroendocrine cells are not required for tumor initiation in a pten knockout mouse prostate cancer model; 4) With the tissue recombination model, tumors can be generated using the neuroendocrine cell-depleted basal cells, suggesting that neuroendocrine cells are incapable of initiating small cell neuroendocrine carcinoma in the tissue recombination model.